: This is a competitive renewal application for a K02 Independent Scientist Award (ISA) from NIDA. The applicant is Eric Strain, a physician-researcher in the Department of Psychiatry at Johns Hopkins University School of Medicine. Dr. Strain has devoted his career to research on drug abuse and to treatment of substance abusing patients, with his primary interest focused upon the development of opioid and cocaine dependence treatment medications. This work has included residential human laboratory studies as well as outpatient clinical trials. There are six short-term and three long-term career goals addressed through the support provided by this ISA. Short-term career goals are: 1) to determine efficacy, safety, and clinical pharmacology of novel substance abuse treatment medications under inpatient experimental conditions, 2) to study efficacy and safety of medications for the treatment of substance abuse disorders utilizing, outpatient clinical trials, 3) to develop and apply methodologies integrating pharmacotherapies with behavioral therapies in clinical trials of substance abuse treatments, 4) to examine the influence of individual characteristics in the course and outcome of substance abuse treatment, 5) to refine expertise in the development process of new medications for the treatment of substance abuse disorders, and 6) to disseminate research findings. Achieving these short-term goals will contribute to accomplishing the first two long-term goals: to contribute new knowledge about the treatment of substance abuse disorder, and to build recognition as an expert in drug abuse treatment and research issues. The final long-term goal is to serve as a mentor and role model for young physicians interested in pursuing a career in substance abuse research. This application's Research Plan provides illustrative investigations that furnish a mechanism for achieving the career goals. These studies examine the pharmacological effects of opioids in human laboratory studies, and test a pharmacotherapy combined with a behavioral therapy in an outpatient clinical trial treating cocaine dependence. This research will be conducted through the Behavioral Pharmacology Research Unit (BPRU), a component of the Hopkins Department of Psychiatry. Dr. Strain has the strong support of the BPRU, the Department of Psychiatry, and the Hopkins School of Medicine, and this ISA provides a mechanism for ensuring the continuation of his highly productive career in substance abuse research. Thus, this ISA represents a good investment by NIDA.